During the past four decades the cigarette consumption in the U.S.A. gradually changed from high-nicotine, high-"tar" to low-nicotine, low- "tar" brands. Concurrently, there was also a gradual shift observed in the major types of cancer and sites within the lung in cigarette smokers. These changes went from predominance of squamous cell carcinoma, located primarily in the bronchi, to adenocarcinoma in the peripheral lung. It is our working hypothesis that the reduction of the smoke yields of U.S. cigarettes and especially that of the addicting nicotine (sales weighted average changed from 2.7 mg in 1955 to 0.85 mg in 1993) resulted in deeper inhalation of the smoke and thus greater exposure of the peripheral lung to cigarette smoke carcinogens. Increased exposure is also to be considered since more intense smoking of low-nicotine cigarettes leads to higher yields of nicotine and certain carcinogens. Four groups of white and African-American male and female smokers of low- (<0.8 mg), medium- (0.8-1.2), and high- (>1.2) nicotine cigarettes will be studied to assess the relationship between their smoking habits and their actual exposure to nicotine, "airborne", and "bloodborne" carcinogens. Currently, the exposure to nicotine and "tar" is assessed on the basis of FTC data. These are established with standard machine-smoking parameters which were developed in 1936. This method does not reflect the smoking habits of today's cigarette smokers. This project together with the risk estimates established in Project 1 for the major types of lung cancer among smokers of cigarettes with low-, medium-, and high-nicotine content, will result, for the first time, in meaningful estimates of exposure to nicotine and to nicotine-derived carcinogens for each of the three classes of cigarettes. The study will also clarify if the low-nicotine cigarette is indeed less "harmful" than the medium- and high-nicotine cigarette. This study has major public health implications. Lung cancer remains the leading cause of cancer death in the U.S.A, while the overall mortality rate from lung cancer continues to rise. Currently, cigarette smoking contributes to more than 90% of the lung cancer deaths in American men and to more than 75% in American women.